Heminth Modulation of Mtb

描述（由申请人提供）：由肺病原体结核分枝杆菌（Mtb）引起的死亡率和发病率仍然高得惊人。已经确定，对Mtb的保护性免疫应答依赖于宿主启动Th1细胞应答的能力。此外，我们也获得了赞赏的机制Th1的发展和微环境的动力学Mtb反应性Thl响应启动。显然，这些研究提供了一些见解宿主保护机制在结核病，但他们没有考虑到的影响，慢性共同流行的传染性病原体可能对结核特异性Th1免疫在人类的发展。世界上结核病发病率高的地区也是蠕虫病的地方。蠕虫感染在宿主中产生强烈的Th2应答。与Th2细胞因子对Th1应答具有抑制作用的事实一起，与蠕虫的共感染极有可能影响TB的发病机制。事实上，人们越来越认识到，控制艾滋病毒、疟疾和结核病这三大传染病的努力需要考虑到，慢性蠕虫感染使受害者更容易受到这三大传染病的影响。在本申请中，我们汇集了Salgame和Gause实验室的专业知识，分别对分枝杆菌和蠕虫感染感兴趣，以检验寄生虫感染改变宿主对结核分枝杆菌的免疫力并调节结核病病程的假设，并确定负责这些影响的免疫机制。目的1将检查在淋巴结中Th1反应的发展，有正在进行的N。brasielinsis（Nb）诱导的Th2应答。目的2将研究在体内的结核病小鼠模型是否与蠕虫共同感染调制tuberculosis diseases.Relevance公共卫生：有越来越多的证据表明，感染寄生虫的人群更容易患结核病。在本申请中，我们将测试寄生虫感染损害宿主抵抗结核病的能力的假设。从这些研究中获得的信息对于疫苗设计和结核病治疗将是重要的。

DESCRIPTION (provided by applicant): Mortality and morbidity caused by the pulmonary pathogen Mycobacterium tuberculosis (Mtb) remains alarmingly high. It is well established that the protective immune response to Mtb is dependent on the host's ability to initiate Th1 cellular responses. In addition, we are also gaining an appreciation for the mechanics of Th1 development and the dynamics of the microenvironment where the Mtb-reactive Thl response is initiated. Clearly these studies are providing some insights into host protective mechanisms in tuberculosis; nevertheless they do not take into account the affect that chronic co-endemic infectious agents may have on the development of Mtb-specific Th1 immunity in humans. Regions of the world with high incidence of Tuberculosis (TB) are also endemic for helminthic diseases. Helminth infections generate a strong Th2 response in the host. Together with the fact that Th2 cytokines have suppressive effects on Th1 responses, it is highly likely that co-infections with helminths may impact on the pathogenesis of TB. There is indeed an enhanced awareness that attempts to control the Big three killers-HIV, Malaria and Tuberculosis- need to take into consideration that chronic helminth infections make their victims more vulnerable to the big three. In this application, we bring together the expertise of the Salgame and Gause laboratories with respective interests in mycobacterial and helminth infections, to test the hypothesis that parasitic infections alter host immunity to Mtb and modulate the course of tuberculosis disease, and to determine the immune mechanisms responsible for these effects. Aim 1 will examine the development of Th1 responses in lymph nodes that have an ongoing N. brasielinsis (Nb)-induced Th2 response. Aim 2 will examine in an in vivo murine model of TB whether co-infection with helminths modulates tuberculosis disease.Relevance to Public health: There is increasing evidence that suggests that populations infected with parasites are more susceptible to tuberculosis. In this application we will test the hypothesis that infection with parasites compromises the host's ability to resist tuberculosis disease. The information obtained from these studies will be important for vaccine design and treatment against tuberculosis/